Congresos y reuniones científicas
Título:
A nanostructure from ascorbyl palmitate based-adjuvant boosts adaptive immunity by inducing an inflammatory effect at the injection site, both properties require the adaptor protein Myd88.
Autor/es:
SANCHEZ-VALLECILLO,MF; ULLO, G; PALMA, S; GONZÁLEZ-CINTADO,L; CHIODETTI, A; AGUIRRE,MV; MORÓN, G; ARDAVIN,C; PISTORESI, MC; MALETTO, B
Reunión:
Congreso; LXII Reunión de la Sociedad Argentina de Inmunología.; 2014
Institución organizadora:
Sociedad Argentina de Inmunología.
Resumen:
The approved adjuvants for human use induce weak cellular
immune responses in subunit vaccines. Thus, the development
of new adjuvant strategies is critical. Recently, we have showed
that a nanostructure from 6-O-ascorbyl palmitate (Coa-ASC16),
used as a platform to formulate CpG-ODN, improved notably its
adjuvanticity; one of the possible mechanisms involved is the
controlled release given by Coa-ASC16 formulation. In addition,
Coa-ASC16 elicits local inflammatory response but how it is
sensed is little understood. Here, we begin to understand the
underlying mechanisms on the interaction between Coa-ASC16
and immune system after i.p injection. We previously found that
the inflammatory response elicited by Coa-ASC16 (neutrophils and
monocytes recruitment and IL-1β, IL-6, IL-12) was dependent on
MyD88 adaptor protein. TLR2, TLR4 and TLR7 were dispensable
for this inflammatory effect. The administration of Coa-ASC16 was
associated with the local release of double-stranded DNA (Coa-
ASC16 vs control 2.5±0.5 vs 0.5±0.1 (μg/mL) (p<0.05)). In mice
injected locally with DNase or in Tlr9-/- mice, the IL-6 production
was inhibited compared to control (pg/mL: 442±167 vs 2231±378
(p<0,001) and 272.4±0.6 vs 1415±322 (p<0.01), respectively).
Coa-ASC16 inflammatory activity is independent of NLRP3 signaling.
In addition, Coa-ASC16 has itself adjuvant activity when
is administrated with OVA antigen, which in turn requires MyD88
and IL-6 cytokine (Myd88-/- vs wt mice: IgG2c: 0.2±0.2 vs 1.6±0.2
(p<0,001), IFN-γ (pg/ml): not detected vs. 931±223; Il6-/- vs wt
mice: IgG2c: 0.1±0.1 vs 2.8±0.5 (p<0.01), IFN-γ (pg/ml): 37±37 vs
254±104 (p<0.05)). Mice immunized with OVA were not reactive.
Our results show a connection, given by IL-6 cytokine, between
the innate and the adaptive response. Coa-ASC16 has not only
a platform capacity but also an adjuvant function. Understanding
the mechanisms of action of this biomaterial is important for development
of safe and effective vaccines.